Copper-Catalyzed Synthesis of Pyridine N-Oxides from α,β-Unsaturated Oximes

Significance

Reported is the synthesis of highly substituted pyridine N-oxides 2 via the copper-catalyzed tandem [2,3]-rearrangement and 6π-3-azatriene electrocyclization of (E)-O-propargylic α,β-unsaturated oximes 1. Alkyl substituents on the oxime fragment were well tolerated. The presence of an electron-withdrawing group on the acetylene (R⁴ = 4-F₃CC₆H₄) led to a moderate yield of 2, whilst the same group at the propargylic position (R^³) led to decomposition of the starting materials. The E-geometry of the oxime is crucial to obtain the pyridine N-oxide, as the Z-stereo­isomer leads to a dihydroisoxazole product via alkylidene group transfer.